Inference of historical population-size changes with allele-frequency data

With up to millions of nearly neutral polymorphisms now being routinely sampled in population-genomic surveys, it is possible to estimate the site-frequency spectrum of such sites with high precision. Each frequency class reflects a mixture of potentially unique demographic histories, which can be revealed using theory for the probability distributions of the starting and ending points of branch segments over all possible coalescence trees. Such distributions are completely independent of past population history, which only influences the segment lengths, providing the basis for estimating average population sizes separating tree-wide coalescence events. The history of population-size change experienced by a sample of polymorphisms can then be dissected in a model-flexible fashion, and extension of this theory allows estimation of the mean and full distribution of long-term effective population sizes and ages of alleles of specific frequencies. Here, we outline the basic theory underlying the conceptual approach, develop and test an efficient statistical procedure for parameter estimation, and apply this to multiple population-genomic datasets for the microcrustacean Daphnia pulex

Differential impact of chronic stress along the hippocampal dorsal–ventral axis

First published online 06 February 2014Stress impacts differently in distinct brain regions. However, so far few studies have focused on the differential responses triggered by stressful stimuli on the intrinsic functional heterogeneity of the hippocampal axis. In this study, we assessed the functional and structural alterations caused by exposure to a chronic unpredictable stress (CUS) paradigm on the dorsal-ventral axis of the hippocampus. The morphological analysis demonstrated that CUS had opposite outcomes in the structure of the dorsal (DH) and ventral hippocampus (VH): whereas in the DH, stress triggered a volumetric reduction as a result of atrophy of CA3 and CA1 apical dendrites, in the VH there was an increase in hippocampal volume concurrent with the increase of CA3 apical dendrites. In parallel, electrophysiological data revealed that stress led to a decrease in VH LTD. In summary, the present work showed that stress impacts differently on the structure and function of the DH and VH which contributes to better understand the overall spectrum of the central effects of stress.Pinto V and Mota C were supported by Fundacao para a Ciencia e Tecnologia (FCT) grants (SFRH/BPD/69132/2010; SFRH/BD/81881/2011, respectively). This work was supported by an FCT grant (PTDC/SAU-NSC/120590/2010). The authors declare no competing financial interests

The Yeast Tor Signaling Pathway Is Involved in G2/M Transition via Polo-Kinase

The target of rapamycin (Tor) protein plays central roles in cell growth. Rapamycin inhibits cell growth and promotes cell cycle arrest at G1 (G0). However, little is known about whether Tor is involved in other stages of the cell division cycle. Here we report that the rapamycin-sensitive Tor complex 1 (TORC1) is involved in G2/M transition in S. cerevisiae. Strains carrying a temperature-sensitive allele of KOG1 (kog1-105) encoding an essential component of TORC1, as well as yeast cell treated with rapamycin show mitotic delay with prolonged G2. Overexpression of Cdc5, the yeast polo-like kinase, rescues the growth defect of kog1-105, and in turn, Cdc5 activity is attenuated in kog1-105 cells. The TORC1-Type2A phosphatase pathway mediates nucleocytoplasmic transport of Cdc5, which is prerequisite for its proper localization and function. The C-terminal polo-box domain of Cdc5 has an inhibitory role in nuclear translocation. Taken together, our results indicate a novel function of Tor in the regulation of cell cycle and proliferation

The effects of purifying selection on patterns of genetic differentiation between Drosophila melanogaster populations.

Using the data provided by the Drosophila Population Genomics Project, we investigate factors that affect the genetic differentiation between Rwandan and French populations of D. melanogaster. By examining within-population polymorphisms, we show that sites in long introns (especially those >2000 bp) have significantly lower π (nucleotide diversity) and more low-frequency variants (as measured by Tajima's D, minor allele frequencies, and prevalence of variants that are private to one of the two populations) than short introns, suggesting a positive relationship between intron length and selective constraint. A similar analysis of protein-coding polymorphisms shows that 0-fold (degenerate) sites in more conserved genes are under stronger purifying selection than those in less conserved genes. There is limited evidence that selection on codon bias has an effect on differentiation (as measured by FST) at 4-fold (degenerate) sites, and 4-fold sites and sites in 8-30 bp of short introns ⩽65 bp have comparable FST values. Consistent with the expected effect of purifying selection, sites in long introns and 0-fold sites in conserved genes are less differentiated than those in short introns and less conserved genes, respectively. Genes in non-crossover regions (for example, the fourth chromosome) have very high FST values at both 0-fold and 4-fold degenerate sites, which is probably because of the large reduction in within-population diversity caused by tight linkage between many selected sites. Our analyses also reveal subtle statistical properties of FST, which arise when information from multiple single nucleotide polymorphisms is combined and can lead to the masking of important signals of selection

The linkage-disequilibrium and recombinational landscape in Daphnia pulex

By revealing the inuence of recombinational activity beyond what can be achieved with controlled crosses, measures of linkage disequilibrium (LD) in natural populations provide a powerful means of defining the recombinational landscape within which genes evolve. In one of the most comprehensive studies of this sort ever performed, involving whole-genome analyses on nearly 1000 individuals of the cyclically parthenogenetic microcrustacean Daphnia pulex, the data suggest a relatively uniform pattern of recombination across the genome. Patterns of LD are quite consistent among populations; average rates of recombination are quite similar for all chromosomes; and although some chromosomal regions have elevated recombination rates, the degree of ination is not large, and the overall spatial pattern of recombination is close to the random expectation. Contrary to expectations for models in which crossing-over is the primary mechanism of recombination, and consistent with data for other species, the distancedependent pattern of LD indicates excessively high levels at both short and long distances and unexpectedly low levels of decay at long distances, suggesting significant roles for factors such as nonindependent mutation, population subdivision, and recombination mechanisms unassociated with crossing over. These observations raise issues regarding the classical LD equilibrium model widely applied in population genetics to infer recombination rates across various length scales on chromosomes

Genome-wide linkage-disequilibrium profiles from single individuals

Although the analysis of linkage disequilibrium (LD) plays a central role in many areas of population genetics, the sampling variance of LD is known to be very large with high sensitivity to numbers of nucleotide sites and individuals sampled. Here we show that a genome-wide analysis of the distribution of heterozygous sites within a single diploid genome can yield highly informative patterns of LD as a function of physical distance. The proposed statistic, the correlation of zygosity, is closely related to the conventional population-level measure of LD, but is agnostic with respect to allele frequencies and hence likely less prone to outlier artifacts. Application of the method to several vertebrate species leads to the conclusion that >80% of recombination events are typically resolved by gene-conversion-like processes unaccompanied by crossovers, with the average lengths of conversion patches being on the order of one to several kilobases in length. Thus, contrary to common assumptions, the recombination rate between sites does not scale linearly with distance, often even up to distances of 100 kb. In addition, the amount of LD between sites separated by <200 bp is uniformly much greater than can be explained by the conventional neutral model, possibly because of the nonindependent origin of mutations within this spatial scale. These results raise questions about the application of conventional population-genetic interpretations to LD on short spatial scales and also about the use of spatial patterns of LD to infer demographic histories